Publication Date

2-24-2023

Journal

Nature Communications

DOI

10.1038/s41467-023-36678-8

PMID

36828809

PMCID

PMC9958016

PubMedCentral® Posted Date

2-24-2023

PubMedCentral® Full Text Version

Post-Print

Published Open-Access

yes

Keywords

Humans, Genome-Wide Association Study, Cholangitis, Sclerosing, Phenotype, Interferon Regulatory Factors, Polymorphism, Single Nucleotide, Genetic predisposition to disease, Genetic variation, Genome-wide association studies

Abstract

Primary sclerosing cholangitis (PSC) is a rare autoimmune bile duct disease that is strongly associated with immune-mediated disorders. In this study, we implemented multitrait joint analyses to genome-wide association summary statistics of PSC and numerous clinical and epidemiological traits to estimate the genetic contribution of each trait and genetic correlations between traits and to identify new lead PSC risk-associated loci. We identified seven new loci that have not been previously reported and one new independent lead variant in the previously reported locus. Functional annotation and fine-mapping nominated several potential susceptibility genes such as MANBA and IRF5. Network-based in silico drug efficacy screening provided candidate agents for further study of pharmacological effect in PSC.

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